Mycophenolate Mofetil in Renal Allograft Recipients

Halloran, Philip F.; Mathew, Timothy H.; Tomlanovich, Stephen J.; Groth, Carl G.; Hooftman, Leon; Barker, C. F.

doi:10.1097/00007890-199701150-00008

Cited by 534 publications

(64 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conversion to Aza was associated with an increase of the rejection rate [14, 311. MMF is a new, promising immunosuppressant for the prevention of allograft rejection and was shown to be superior to AZA [12]. Nephrotoxity is also not a prominent feature of MMF [30].…”

Section: Discussionmentioning

confidence: 99%

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity

et al. 2000

View full text Add to dashboard Cite

Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a nonnephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal transplant recipients (10.8 f 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 k 2.7 (range 2.3-11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 the time of conversion (188 f 100 pmol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 t 69 pmolil ( P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 * 39 mg/ m2 per day to 59 f 13 mg/m2 per day 96 pmol/l, lower than at in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1-18 months). After a median period of 21 days, a pharrnacokinetic profile was performed in all patients. The mean MMF dose was 1117 f 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 k 2.0 pg/ml, range 1.4-7.9 pg/ml. Mean 12 h MPA AUC was 70.6 k 28.1 (range 31.9-127) pg x h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2 per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The ability of MMF (2 g/day or 3 g/day) to control biopsy-proven acute rejection episodes during the first 6 months post transplantation was compared to either azathioprine or a placebo, combined with a maintenance regimen of full-dose cyclosporine and a corticosteroid. 13 The results in all three studies were similar. 14 In a pooled analysis of efficacy, MMF was shown to reduce the incidence, as well as the histologically graded severity of acute rejection episodes by approximately 50%.…”

Section: Efficacy In Solid Organ Transplantationmentioning

confidence: 59%

“…14 In a pooled analysis of efficacy, MMF was shown to reduce the incidence, as well as the histologically graded severity of acute rejection episodes by approximately 50%. 13 It also significantly reduced the need for antithymocyte globulin (ATG) to treat severe, corticosteroid-resistant rejection. 13 Use of MMF in cardiac allograft recipients was studied in a multicenter trial of 650 patients randomized to receive MMF 3 g/d, azathioprine, or placebo, in combination with full-dose cyclosporine and a corticosteroid.…”

Section: Efficacy In Solid Organ Transplantationmentioning

confidence: 99%

“…13 It also significantly reduced the need for antithymocyte globulin (ATG) to treat severe, corticosteroid-resistant rejection. 13 Use of MMF in cardiac allograft recipients was studied in a multicenter trial of 650 patients randomized to receive MMF 3 g/d, azathioprine, or placebo, in combination with full-dose cyclosporine and a corticosteroid. 15 The 1-year mortality was 45% lower in the MMF treatment group than in the azathioprine treatment group.…”

Section: Efficacy In Solid Organ Transplantationmentioning

confidence: 99%

See 1 more Smart Citation

Mycophenolate mofetil for the prevention and treatment of graft-versus-host disease following stem cell transplantation: preliminary findings

Vogelsang¹,

Arai²

2001

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:The therapeutic benefits of allogeneic stem cell transplantation in patients with hematologic disorders are limited by the significant morbidity and mortality of graft-versus-host disease (GVHD). Current agents for the prevention and treatment of GVHD have limited efficacy and often result in toxic side-effects. Mycophenolate mofetil (MMF) is a new immunosuppressant with a selective mechanism of action. When employed following solid organ transplantation, MMF reduces the incidence and severity of acute rejection episodes. By selectively targeting activated lymphocytes, the active metabolite of MMF, mycophenolic acid (MPA), appears to augment the actions of standard immunosuppressant agents without adding overlapping toxicities. Studies of combination regimens that include MMF report that this agent permits a dose reduction of cyclosporine, tacrolimus, or corticosteroid, without increasing the incidence of acute rejection in solid organ transplants. Reports on the efficacy of MMF following stem cell transplantation in animal studies were mixed. However, the use of a non-myeloablative conditioning regimen with a post-graft immunosuppressive regimen of MMF and cyclosporine was able to sustain stable mixed chimeras in 60% to 80% of dogs who received hematopoietic grafts from DLA-identical littermates. MMF has demonstrated activity in preliminary clinical trials for GVHD prophylaxis, and treatment of acute or chronic GVHD. Larger clinical trials are warranted to determine the optimum dose and route of MMF administration for GVHD, as well as the comparative safety and efficacy of MMF-containing regimens. Allogeneic stem cell transplantation (SCT) has significant therapeutic benefits for many patients with hematologic disorders. Unfortunately, the benefits of the stem cell graft are limited by the significant morbidity and mortality of graftversus-host disease (GVHD). 1 In related donor, histocompatible-matched, and unmanipulated allografts, acute GVHD develops in approximately 30% to 60% of SCT recipients; when the donor and recipient are unrelated or histoincompatible, the prevalence is higher, from 40% to 90%. 2,3 Mortality, as a direct or indirect consequence of acute GVHD, may be as high as 50%. 2 In addition, chronic GVHD develops in 35% to 50% of long-term survivors. 2 Current post-transplantation therapies to prevent or treat GVHD are only partially effective. Furthermore, these immunosuppressive regimens often result in significant toxicities. With cyclosporine therapy, the prevalence of nephrotoxicity can be as high as 75%. 4 Long-term use of glucocorticoids increases the risk of hyperglycemia, infections, avascular necrosis of bone, and osteoporosis. 2,4 The therapeutic index for methotrexate (MTX) is extremely low, and the occurrence of hyperbilirubinemia, bone marrow suppression, or mucositis is common. 4,5 There is an obvious need for new immunosuppressive strategies that provide greater control of GVHD with less toxicity. Mycophenolate mofetil (MMF) is an immunosuppressant presently used for the ...

show abstract

“…Prostate cancer regions that are missed on repeat biopsy are often located in the apicaldorsal region of the peripheral zone [18]. Endorectal MRI is more accurate than biopsy in locating intraprostatic tumour at the apex [19]. Pelvic CT is indicated for detecting lymphadenopathy, but not for intraprostatic tumour because of its low soft-tissue contrast [17].…”

mentioning

confidence: 99%

Correct answers to multiple choice questions appearing in the European Urology Update Series 2002

2003

BJU International

View full text Add to dashboard Cite

Mycophenolate Mofetil in Renal Allograft Recipients

Abstract: MMF proved superior to AZA as a posttransplant immunosuppressant in conjunction with cyclosporine and corticosteroids. MMF-treated groups showed reduced incidence and severity of rejection episodes, similar graft survival, and better graft function over 12 months.

Cited by 534 publications

References 11 publications

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity

Mycophenolate mofetil for the prevention and treatment of graft-versus-host disease following stem cell transplantation: preliminary findings

Correct answers to multiple choice questions appearing in the European Urology Update Series 2002

Contact Info

Product

Resources

About